Effective absorption rate constant

This may be concentration and drug dependent, f = Increase, = decrease, — = no effect, = absorption rate constant, drug concentration time curve. 

The absorption number (An) is the ratio of permeability (Peff) and the intestinal radius (P) multiplied by the residence time (t,.es), which can be interpreted as the effective absorption rate constant (t. ) times the residence time ... 

The absorption rate constant Ka can be estimated from the effective permeability ... 

The first-order absorption rate constant introduced above may be directly related to the effective permeability coefficient (Peff) using... 

Fig. 2.6 Effect of variation in absorption rate on plasma drug concentration. The graph shows simulated plasma concentration-time curves for theophyUine after oral administration, illustrating a 20% difference in Cpmax values resulting from variation in the absorption rate constant. Absorption rate constants top curve 2.2 per h (Cpmax 20 pg/mL) middle curve 1.0 per h (Cptnax 18 M-g/mL) bottom curve 0.7 per h. Note that tmax also changes. The established therapeutic concentration of theophyUin is 10-20 pg/mL. The most rapidly absorbed formulation produces the highest concentration and greatest chance of side effects. Also, the duration for which the plasma concentration is within the therapeutic range also varies. Pharmacokinetic parameters dose, 400 mg bioavaUabiUty, 0.8 volume of distribution, 29 L half-Ufe, 5.5 h.

The drawbacks of SC and IM injections include potentially decreased bioavailability that is secondary to variables such as local blood flow, injection trauma, protein degradation at the site of injection, and limitations of uptake into the systemic circulation related to effective capillary pore size and diffusion. The bioavailability of numerous peptides and proteins is, for example, markedly reduced after SC or IM administration compared to their IV administration. The pharmacokine-tically derived apparent absorption rate constant is thus the combination of absorption into the systemic circulation and presystemic degradation at the absorption site. The true absorption rate constant ka can then be calculated as ... 

An example of the correlations obtained in small intestine in the absence and in the presence of tetradecyltrimethylamonium bromide (TTAB) at 0.0125% (CMC) is represented in Fig. 4.4 [26]. As can be seen, the effect of each surfactant concentration is quite significant. But, a natural surfactant such as sodium taurocholate did not produce any significant change in the absorption rate constants of a series of phenyl-alkyl carboxylic acids at its CMC and it exerted an almost negligible solubilization effect at a supramicellar concentration [23]. 

Figure 11 Effect of varying absorption rate constant (ka) on the concentration time plots for two hypothetical drugs with similar dose, bioavailability, clearance, and volume of distribution. Case 1 (smooth line) ka > ke and Case 2 (broken line) ka < ke (flip-flop situation).

A proportional error, a constant additive error, and a combination of both error models were evaluated for the residual error model. Between-subject random effects were explored on the clearance of parent drug and metabolite, the volume of distribution of the parent drug, and the absorption rate constant. An exponential model was preferred. Interoccasion random effects were explored on the clearance of the parent drug and of the metabolite, the volume of distribution of the parent drug, and the absorption rate constant. An exponential model was preferred. The joint distribution of the between-subject random effect, the interoccasion random effects, and the residual error were assumed normal with mean 0 and variance-covariance matrices O for the between-subject and interoccasion random effects, and I, for the residual error to be estimated. The FO method was used for the estimation of the parameters. 

Both between-subject and interoccasion variances were estimated on clearance of nelfinavir, absorption rate constant, and clearance of M8. The residual error with a proportional error model was modeled for nelfinavir and M8 separately. The effect of ritonavir was found to have a statistically significant impact on the clearance of M8 but not on that of nelfinavir. The apparent clearance of M8 was 3.23 L/h it decreased to 1.87 L/h when nelfinavir was coadministered with ritonavir. After univariate selection, a large number of covariates were included in the full model. According to the acceptance criteria, none of the effect on clearance of nelfinavir on... 

To simplify matters we will also assume that most of the absorption of photons by the tumor occurs in a thin region near L. We can then practically model this process as a surface reaction with a rate = —ksurface rate constant that has units of length/time. Thus the flux of incident photons into the tumor is equal to the rate of consumption by the surface reaction. Note that, for every photon absorbed by the tumor, we assume that a fluorescent photon of a different wavelength is emitted toward the surface of the skin. Further, the number of density of fluorescent photons at the surface of the skin is negligibly small. (The last two boundary conditions are reasonable, simplifying approximations, but in fact not the most accurate. However, they are quite suitable for our purposes.) Our objective is to determine the flux of these emitted photons and how its frequency response can be used to locate the depth of the tumor. 

What is not immediately apparent from Eq. 6.15 is that a small value of either the absorption rate constant (as may occur in a poor oral formulation) or of the elimination rate constant (as may be the case in a renally impaired patient) will have the effect of lengthening the peak time and slowing the onset of action. This may be proved by changing the value of one parameter at a time in Eq. 6.15. 

In 6 healthy subjects, oral salbutamol 4 mg four times daily for 2 weeks had no elTect on the pharmacokinetics of a single 400-mg oral dose of sulfamethoxazole (in co-trimoxazole), although the absorption rate constant was reduced by about 40% and the extent of absorption over 72 hours was increased by 22.6%. A possible reason for these effects is that salbutamol stimulates the beta receptors in the gut, causing relaxation, which allows an increased contact time, and therefore increased absorption of sulfamethoxazole. The clinical significance of this interaction is unknown, but it... 

Section BT1.2 provides a brief summary of experimental methods and instmmentation, including definitions of some of the standard measured spectroscopic quantities. Section BT1.3 reviews some of the theory of spectroscopic transitions, especially the relationships between transition moments calculated from wavefiinctions and integrated absorption intensities or radiative rate constants. Because units can be so confusing, numerical factors with their units are included in some of the equations to make them easier to use. Vibrational effects, die Franck-Condon principle and selection mles are also discussed briefly. In the final section, BT1.4. a few applications are mentioned to particular aspects of electronic spectroscopy. 

With M = He, experimeuts were carried out between 255 K aud 273 K with a few millibar NO2 at total pressures between 300 mbar aud 200 bar. Temperature jumps on the order of 1 K were effected by pulsed irradiation (< 1 pS) with a CO2 laser at 9.2- 9.6pm aud with SiF or perfluorocyclobutaue as primary IR absorbers (< 1 mbar). Under these conditions, the dissociation of N2O4 occurs within the irradiated volume on a time scale of a few hundred microseconds. NO2 aud N2O4 were monitored simultaneously by recording the time-dependent UV absorption signal at 420 run aud 253 run, respectively. The recombination rate constant can be obtained from the effective first-order relaxation time, A derivation analogous to (equation (B2.5.9). equation (B2.5.10). equation (B2.5.11) and equation (B2.5.12)) yield... 

Morishima et al. [75, 76] have shown a remarkable effect of the polyelectrolyte surface potential on photoinduced ET in the laser photolysis of APh-x (8) and QPh-x (12) with viologens as electron acceptors. Decay profiles for the SPV (14) radical anion (SPV- ) generated by the photoinduced ET following a 347.1-nm laser excitation were monitored at 602 nm (Fig. 13) [75], For APh-9, the SPV- transient absorption persisted for several hundred microseconds after the laser pulse. The second-order rate constant (kb) for the back ET from SPV- to the oxidized Phen residue (Phen+) was estimated to be 8.7 x 107 M 1 s-1 for the APh-9-SPV system. For the monomer model system (AM(15)-SPV), on the other hand, kb was 2.8 x 109 M-1 s-1. This marked retardation of the back ET in the APh-9-SPV system is attributed to the electrostatic repulsion of SPV- by the electric field on the molecular surface of APh-9. The addition of NaCl decreases the electrostatic interaction. In fact, it increased the back ET rate. For example, at NaCl concentrations of 0.025 and 0.2 M, the value of kb increased to 2.5 x 108 and... 

For chemical reaction-rate constants greater than 10 sec-1, NT increases linearly with the total bubble surface area, i.e., linearly with the gas holdup. In other words, the agitation rate only affects the total bubble surface area and has almost no effect on the rate of absorption per unit area. This result is in accordance with the work of Calderbank and Moo-Young (C4), discussed in Section II. 

The overall reaction between CO2 and GMA was assumed to consist of two elementary reactions such as a reversible reaction of GMA and catalyst to form an intermediate and an irreversible reaction of this intermediate and carbon dioxide to form five-membered cyclic carbonate. Absorption data for CO2 in the solution at 101.3 N/m were interpreted to obtain pseudo-first-order reaction rate constant, which was used to obtain the elementary reaction rate constants. The effects of the solubility parameter of solvent on lc2/k and IC3 were explained using the solvent polarity. 

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